Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) and Thyroid Function in Childhood Obesity: A Vicious Circle?

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a multisystem disorder characterized by the presence of fatty liver degeneration associated with excess adiposity or prediabetes/type 2 diabetes or metabolic dysregulation. An intricate relationship between the liver and thyroid has been reported in both health and disease. Simultaneously, there is a strong correlation between obesity and both MAFLD and thyroid dysfunction. In this narrative review, we highlighted the relationship between MAFLD and thyroid function in children and adolescents with obesity in order to explore how thyroid hormones (THs) act as predisposing factors in the onset, progression, and sustainability of MAFLD. THs are integral to the intricate balance of metabolic activities, ensuring energy homeostasis, and are indispensable for growth and development. Regarding liver homeostasis, THs have been suggested to interact with liver lipid homeostasis through a series of processes, including stimulating the entry of free fatty acids into the liver for esterification into triglycerides and increasing mitochondrial ß-oxidation of fatty acids to impact hepatic lipid accumulation. The literature supports a correlation between MAFLD and obesity, THs and obesity, and MAFLD and THs; however, results in the pediatric population are very limited. Even though the underlying pathogenic mechanism involved in the relationship between MAFLD and thyroid function remains not fully elucidated, the role of THs as predisposing factors of MAFLD could be postulated. A potential vicious circle among these three conditions cannot be excluded. Identifying novel elements that may contribute to MAFLD could offer a practical approach to assessing children at risk of developing the condition.

Prader-Willi Syndrome and Weight Gain Control: From Prevention to Surgery-A Narrative Review.

Severe obesity remains one of the most important symptoms of Prader-Willi Syndrome (PWS), and controlling weight represents a crucial point in the therapeutical approach to the syndrome. We present an overview of different progressive patterns of growth that involve controlling weight in PWS. Mechanisms involved in the development of obesity and in preventive and therapeutic strategies to control weight gain are discussed. Early diagnosis, a controlled diet regimen, regular physical activity, follow-up by multidisciplinary teams, and hormonal treatment improved the management of excessive weight gain. In selected cases, a surgical approach can be also considered. Controlling weight in PWS remains a challenge for pediatricians. The importance of consulting different healthcare specialists, starting from the neonatal and pediatric age, is also considered as a crucial approach to controlling weight, as well as to limiting and preventing the onset of obesity and its complications.

Childhood Obesity and Incorrect Body Posture: Impact on Physical Activity and the Therapeutic Role of Exercise.

Obesity is associated with various dysfunctions of the organism, including musculoskeletal problems. In this narrative review, we aim to consider postural problems in children and adolescents with obesity, focusing on the relationship with its negative impact on physical activity, and to discuss the role of exercise as a therapeutic approach. The body reacts to excess weight by changing its normal balance, and the somatosensory system of children with obesity is forced to make major adjustments to compensate for postural problems. These adaptations become more difficult and tiring if activities that require continuous postural changes and multi-tasking are engaged in. Children with obesity have less body control and functional ability due to the excess fat mass, which reduces their ability to perform motor skills and take part in physical activity. Appropriate early interventions for the management of musculoskeletal problems are needed to ensure healthy growth and to prevent comorbidities in childhood and adulthood. Prevention programs must be based not only on the reduction of body weight but also on the definition of correct postural habits from an early age. It is equally important to provide correct information on the types and doses of physical activity that can help prevent these problems.

Benefits of Physical Exercise as Approach to Prevention and Reversion of Non-Alcoholic Fatty Liver Disease in Children and Adolescents with Obesity.

Non-alcoholic fatty liver disease (NAFLD) is an important health concern during childhood; indeed, it is the most frequent cause of chronic liver diseases in obese children. No valid pharmacological therapies for children affected by this condition are available, and the recommended treatment is lifestyle modification, usually including nutrition and exercise interventions. In this narrative review, we summarized up-to-date information on the benefits of physical exercise on NAFLD in children and adolescents with obesity. The role of exercise as non-pharmacological treatment was emphasized in order to provide recent advances on this topic for clinicians not deeply involved in the field. Several studies on obese children and adults confirm the positive role of physical activity (PA) in the treatment of NAFLD, but to date, there are no pediatric randomized clinical trials on exercise versus usual care. Among the pathogenic mechanisms involved in the PA effects on NAFLD, the main players seem to be insulin resistance and related inflammation, oxidative stress, and gut dysbiosis, but further evaluations are necessary to deeply understand whether these factors are correlated and how they synergistically act. Thus, a deeper research on this theme is needed, and it would be extremely interesting.

Management of Metastatic Disease in Campania (MAMETIC): An Observational Multicenter Retrospective and Prospective Trial on Palliative Radiotherapy in an Italian Region. Study Protocol.

Background: In the Italian Campania Region, 30.517 new cases of solid cancer have been diagnosed, in 2019. Of those, patients with metastatic disease are up to 20%. This class of patients is extremely diversified and copious, and the offer of radiotherapy may vary in different geographical areas within the same region. The aim of this observational multicenter retrospective and prospective trial is to evaluate the occurrence of metastatic metastatic cancer patients candidates for palliative radiotherapy in several areas of a great Italian region, the management of the disease through RT approaches, and its impact on cancer-related pain and overall HRQoL. Methods: This is a multicenter, retrospective and prospective observational investigation. The retrospective part of the study concerns all patients enrolled with a diagnosis of metastatic disease and treated in RT centers within the Campania Region between January 2019 and July 2020. The prospective phase is going to involve all the metastatic patients with an indication of palliative RT. Considering regional epidemiological data, we expect an enrollment of 12.500-21.000 patients in 5 years. Conclusion: The MAMETIC Trial in an observational study designed for investigating on the use of radiotherapy in patients with advanced disease within a regional area, and for evaluating the local response to the patient's request. It can be a unique opportunity, not only to highlight possible geographic differences but also to regularly collect and share data to standardize the therapeutic offer within the regional area. ClinicalTrials.gov ID NCT04595032, retrospectively registered.

Validation of DWI in assessment of radiotreated bone metastases in elderly patients.

Bone metastases are commonly observed in oncologic patients with advanced disease. These metastases are considered the main cause of neoplastic pain, with more than half of oncologic patients experiencing neoplastic pain during the course of the disease due to bone involvement. Lung, breast, and prostate cancers are the primary causes of bone metastases. Magnetic resonance imaging (MRI), especially diffusion weighted imaging (DWI) sequences, is the focus of our research, as it has been proven to be an optimal predictive index to assess the radiation treatment in many patients. We included patients treated with standard fractioning of radiation therapy. First, we examined the irradiated lesions with the MRI-DWI technique, before treatment and 30 and 60 days after its completion. Then we combined the MRI results and clinical parameters in a table with a predictive score for the quality of life in patients with bone metastases. This was a significant predictor of the efficacy of radiation treatment, from both clinical and psychological points of view, as it can allow an early assessment of the response to RT and therefore better scheduling of the next therapeutic steps to be performed. The table of the score we proposed helped guide patient monitoring, enabling us to undertake, where possible, follow-up with therapeutic strategies tailored to each patient's needs.

Performance status versus anatomical recovery in metastatic disease: The role of palliative radiation treatment.

Metastatic disease is a common complication of the most advanced malignancies. It may compromise the patients' quality of life, often posing a greater risk than the primary disease itself. Currently, several different therapeutic approaches are available to palliate or cure (single metastasis with primary neoplasm under control - radical surgery) secondary disease. In particular, radiation therapy is widely used, as it often leads to full or at least partial functional recovery, depending on the number and location of metastases. The aim of our study was to evaluate whether clinical improvement subsequent to radiation therapy may be related to anatomical recovery of the site of metastasis in cancer patients with metastatic disease. Given the heterogeneity of the diseases considered and the general complex conditions of the patients, a single method could not be used to evaluate the response to radiation treatment and its correlation with the performance status (PS). Thus, depending on the specific disease being assessed, we divided the patients into different groups. Patients in the same group were followed up with the same methods. This correlation was noted in a very high percentage of patients, predominantly in patients with vertebral and brain metastases. Moreover, we investigated the use of magnetic resonance imaging (MRI)-diffusion weighted imaging (DWI) in the study of spinal metastases. We propose its use in the local evaluation of vertebral secondary lesions, both in the diagnostic phase and during the assessment of treatment efficacy.

Management of breast cancer in elderly patients.

Even if there is not a general consensus, we consider elderly patients of 65 years old or more. The degree of aging is extremely variable so that we can individuate different groups of patients that are different one from the other in relation with Performance Status, the presence of other pathology, and of eventual social discomfort. Breast Cancer is the most common Tumor in elderly woman and it represent the first death cause The 45% of Breast Cancer arise in women more than 65 years old and the 33% arise in women of more than 70 years old. Despite these data elderly women are often excluded from screening schedules, moreover despite there is no evidence that breast cancer is less aggressive in elderly patient they are generally non considered in trial studies so that they are under treated if compared to young patients that's why we cannot observe a decrease of mortality such as in younger patients Relative survival between 5 and 10 years in patients more than 75 years old it's lesser than the one observed in younger patients (between 45 and 70 years old) maybe that's because of the incongruity in the access to sanitary structures and because of the social and economic discomfort. When we speak about Breast Cancer we cannot be able to leave a multidisciplinary approach out of consideration. Patient's evaluation must be done by a group of dedicated specialists that are: Radiologist, Pathologist, Surgeon, Radiotherapist and Oncologist. The team need to analyze all data to improve treatment and obtain a better cosmetic result [4]. Complex cases must be discussed collectively before surgery to obtain the best therapeutic strategy. Moreover it's strictly important patient's involvement in treatment selection. Consensus is mandatory and it can be obtained only if the patient is well informed about treatment phases, adverse effects, and results.

Use of adjuvant therapy in patients with FIGO stage III endometrial carcinoma: a multicenter retrospective study.

OBJECTIVES: Adjuvant treatment for stage III endometrial cancer is not yet defined. Previous experiences support the usefulness of combined chemotherapy and radiotherapy. The aim of this retrospective study was to describe the outcome in a cohort of patients with stage III endometrial cancer treated with chemotherapy and/or radiotherapy. METHODS: A multicenter retrospective analysis of patients with stage III endometrial cancer from 1998 to 2009 was conducted. The impact on relapse-free survival of clinical and pathological variables and adjuvant treatment received was analyzed by univariate and multivariate analysis. RESULTS: Eighty-two patients were considered. Median age was 62 years (range 38-82). Seventy-eight (95%) patients received an adjuvant treatment: chemotherapy (41; 50%), radiotherapy (18; 22%), or combined chemo-radiotherapy (19; 23%). Four patients were excluded from analysis because they were not treated with any adjuvant therapy. At univariate analysis, tumor grade (G3 vs. G1-G2; p = 0.003) was associated with risk of recurrence; similarly, patients treated with radiotherapy alone (p = 0.031, hazard ratio 0.19, 95% CI 0.04-0.86) or chemotherapy alone (p = 0.053, hazard ratio 0.54, 95% CI 0.29-1.01) had a significantly higher risk for relapse, compared to those treated with the multimodality approach. Relapse-free survival at 3 years was 86.5, 65.8 and 44.1%, with the multimodality approach, chemotherapy and radiotherapy, respectively. At multivariable analysis, age and grading were independently associated with recurrence-free survival. Hazard ratio for relapse-free survival was 0.14 (95% CI 0.02-1.04) and 0.20 (95% CI 0.04-1.11) for multimodality treatment compared to chemotherapy alone and radiotherapy alone, respectively. CONCLUSIONS: Age and grading are independent prognostic factors. A combined approach with radiotherapy and chemotherapy may induce an advantage in relapse-free survival compared to radiotherapy or chemotherapy alone. Prospective clinical trials are needed to verify this clinical hypothesis.

Bladder-sparing, combined-modality approach for muscle-invasive bladder cancer: a multi-institutional, long-term experience.

BACKGROUND: The authors evaluated their long-term experience with combined-modality, conservative treatment in patients with muscle-invasive bladder cancer. METHODS: In total, 121 patients with T2, T3, or T4 bladder cancer (mean age, 63 years; ratio of men to women, 3:1) underwent induction by transurethral resection (TUR) of the tumor and received 2 cycles of neoadjuvant chemotherapy followed by radiotherapy (RT) (n = 43 patients) or radiochemotherapy (RCT) (n = 78 patients). Six weeks after RT or RCT, responses were evaluated by restaging TUR. Patients who achieved a complete response (CR) were observed at regular intervals. In patients who had persistent or recurrent invasive tumor, further treatment was recommended. RESULTS: Local response evaluation by restaging TUR was possible in 119 patients, and 102 of those patients (85.7%) achieved a CR. After a median follow-up of 66 months (range, 6-182 months), no local or distant disease recurrences were observed in 67 of 102 complete responders (65.7%), 17 of 102 complete responders (16.7%) experienced superficial local disease recurrence, and 18 of 102 complete responders (17.6%) had a muscle-invasive relapse. The 5-year tumor-specific, overall, and bladder-intact survival rates were 73.5%, 67.7%, and 51.2%, respectively. Treatment modality, tumor classification, and resection status after initial TUR had an impact on survival rates (P = .04, P = .02, and P = .02, respectively). CONCLUSIONS: The current results indicated that conservative combined treatment is a reasonable alternative to radical cystectomy in selected patients with muscle-invasive bladder cancer.

Significance of erb-B2 immunoreactivity in cervical cancer.

C-erbB2 is over-expressed or amplified in many carcinomas. We assessed the relationship between erb-B2 immunoreactivity, and its predictive role in progression-free survival and treatment outcome in patients with cervical carcinoma. Sections from 65 cervical carcinoma were immunostained with antibody to p185 erbB2. Immunoreactive ErbB2 was found in 25 patients (38%) [+ 15 pts. (23%); ++ 10 pts. (15%)]. There were no correlation with age, performance status, grading and histology. Erb-B2 immunoreactivity significantly correlated with stage of the disease. Positive immunoreactivity was found in 63%, 44%, 14% and 0% of stage I, II, III and IV carcinomas, (p = 0.0045). Progression-free survival was longer in erb-B2 positive patients without reaching significance. No correlation was found between erbB2 and response to radiotherapy or chemotherapy. In conclusion, a significant proportion of stage I and II cervical cancer express erb-B2 compared to more advanced stages. Expression of the oncogene does not appear to be related to prognosis or treatment outcome.

Malignant glomus tumour: a case report and review of the literature.

PURPOSE: Glomus tumours are characteristically benign solitary tumours. At our knowledge, about 23 reports are present in literature regarding the malignant counterpart, but only a minority developed metastases. We describe a locally aggressive glomus tumour with lymphnode metastasis. PATIENT: The patient was a 40 year-old man presenting a 1.5-cm lesion on the right wrist incompletely excised and a recurrent tumour, 4 x 2 cm in size, removed after 9 months, for which he received radiotherapy. After 2 years he developed an axillary lymphnode metastasis. RESULTS: Histologically, both tumours (primary and metastasis) were similar. There were sheets and nests of uniform small cells with scant eosinophilic cytoplasm and round to polygonal nuclei; there was some degree of pleomorphism and the mitotic index was high (up to 18 m/10 HPF). The tumour cells were positive for vimentin and smooth muscle actin, but negative for desmin, NSE, Factor VIII, chromogranin, cytokeratin. Remarkably, in the primary, the cells strongly expressed p53 (70%) and MIB-1 (35%). DISCUSSIONS: In many reported malignant cases, the histology of the tumour cells suggested that they were malignant, yet the clinical course has been benign. Carefully reviewing the literature, it seems that actually we have enough histological criteria to identify the cases with biological adverse outcome. Those unfortunate cases behave as high grade sarcomas and therefore may deserve an aggressive therapeutic treatment.